title: The Influence of Hepatitis B Viral Load and Pre-S Deletion Mutations on Post-Operative Recurrence of Hepatocellular Carcinoma and the Tertiary Preventive Effects by Anti-Viral Therapy.
abstract: Whether or not hepatitis B virus (HBV) genotypes, mutations, and viral loads determine outcomes for patients with HBV-induced hepatocellular carcinoma (HCC) remains controversial.
  
  
  
  To study the influence of HBV viral factors on prognoses for patients with HBV-induced HCC after resection surgery and investigate if antiviral therapy could counteract the adverse effects of viral factors.
  
  
  
  A total of 333 HBV-related HCC patients who underwent tumor resection were enrolled retrospectively. Serum HBV DNA levels, mutations, anti-viral therapy, and other clinical variables were analyzed for their association with post-operative recurrence.
  
  
  
  After a median follow-up of 45.9 months, 208 patients had HCC recurrence after resection. The 5-year overall survival and recurrence-free survival rates were 55.4% and 35.3%, respectively. Multivariate analysis showed indocyanine green retention rate at 15 minutes >10%, gamma-glutamyltransferase (GGT) level >60 U/L, macroscopic and microscopic venous invasion, and the absence of anti-viral therapy were significant risk factors for recurrence. Anti-viral therapy could decrease recurrence in patients with early stage HCC, but the effect was less apparent in those with the Barcelona-Clinic Liver Cancer stage C HCC. For patients without antiviral therapy after resection, serum HBV DNA levels >10(6) copies/mL, GGT >60 U/L, and macroscopic and microscopic venous invasion were significant risk factors predicting recurrence. Among the 216 patients without anti-viral therapy but with complete HBV surface gene mapping data, 73 were with pre-S deletion mutants. Among patients with higher serum HBV DNA levels, those with pre-S deletion had significantly higher rates of recurrence. Moreover, multivariate analysis showed multi-nodularity, macroscopic venous invasion, cirrhosis, advanced tumor cell differentiation, and pre-S deletion were significant risk factors predictive of recurrence.
  
  
  
  Ongoing HBV viral replication and pre-S deletion are crucial for determining post-operative tumor recurrence. Anti-viral therapy can help reduce recurrence and improve prognosis, especially for those with early stage HCC.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan ; Faculty of Medicine, Cancer Research Center, National Yang-Ming University, Taipei, Taiwan ; Institute of Clinical Medicine, Cancer Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chien-Wei
authors.initials: CW
authors.lastname: Su
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Chiou
authors.forename: Yi-Hsuan
authors.initials: YH
authors.lastname: Tsai
authors.forename: Ruei-Dun
authors.initials: RD
authors.lastname: Teng
authors.forename: Gar-Yang
authors.initials: GY
authors.lastname: Chau
authors.forename: Hao-Jan
authors.initials: HJ
authors.lastname: Lei
authors.forename: Hung-Hsu
authors.initials: HH
authors.lastname: Hung
authors.forename: Teh-Ia
authors.initials: TI
authors.lastname: Huo
authors.forename: Jaw-Ching
authors.initials: JC
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000235:genetics / Q000601:surgery / Q000821:virology; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006509:Hepatitis B / Q000097:blood / Q000235:genetics / Q000628:therapy; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000235:genetics / Q000601:surgery / Q000821:virology; D008297:Male; D008875:Middle Aged; D017384:Sequence Deletion; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens